Maternal Reinfection Research Articles

Maternal Cytomegalovirus Reinfection during Pregnancy among Women Living with HIV

Maternal Cytomegalovirus Reinfection during Pregnancy among Women Living with HIV

Relationship of maternal cytomegalovirus-specific antibody responses and viral load to vertical transmission risk following primary maternal infection in a rhesus macaque model.

Cytomegalovirus (CMV) is the most common congenital infection and cause of birth defects worldwide. Primary CMV infection during pregnancy leads to a higher frequency of congenital CMV (cCMV) than maternal re-infection, suggesting that maternal immunity confers partial protection. However, poorly understood immune correlates of protection against placental transmission contributes to the current lack of an approved vaccine to prevent cCMV. In this study, we characterized the kinetics of maternal plasma rhesus CMV (RhCMV) viral load (VL) and RhCMV-specific antibody binding and functional responses in a group of 12 immunocompetent dams with acute, primary RhCMV infection. We defined cCMV transmission as RhCMV detection in amniotic fluid (AF) by qPCR. We then leveraged a large group of past and current primary RhCMV infection studies in late-first/early-second trimester RhCMV-seronegative rhesus macaque dams, including immunocompetent (n = 15), CD4+ T cell-depleted with (n = 6) and without (n = 6) RhCMV-specific polyclonal IgG infusion before infection to evaluate differences between RhCMV AF-positive and AF-negative dams. During the first 3 weeks after infection, the magnitude of RhCMV VL in maternal plasma was higher in AF-positive dams in the combined cohort, while RhCMV glycoprotein B (gB)- and pentamer-specific binding IgG responses were lower magnitude compared to AF-negative dams. However, these observed differences were driven by the CD4+ T cell-depleted dams, as there were no differences in plasma VL or antibody responses between immunocompetent AF-positive vs AF-negative dams. Overall, these results suggest that levels of neither maternal plasma viremia nor humoral responses are associated with cCMV following primary maternal infection in healthy individuals. We speculate that other factors related to innate immunity are more important in this context as antibody responses to acute infection likely develop too late to influence vertical transmission. Yet, pre-existing CMV glycoprotein-specific and neutralizing IgG may provide protection against cCMV following primary maternal CMV infection even in high-risk, immunocompromised settings.

The crucial role of the partner in the incidence of cases of congenital syphilis in the state of Sergipe: an analysis in 17 years

Introduction: Congenital syphilis is a highly preventable infectious disease. The relevance of the partner in the transmission of the disease is undeniable, and the underestimation of its treatment is a great risk with serious fetal consequences. Objective: The aim of this study was to analyze the partner’s contribution to the inadequate treatment of pregnant women and the incidence of cases of congenital syphilis in Sergipe between 2005 and 2022. Methods:A cross-sectional, retrospective, and descriptive study was carried out through the collection of reported cases of congenital syphilis from the Notifiable Diseases Information System (SINAN). Results: There was a considerable increase in the number of reported cases of congenital syphilis in Sergipe in the past 17 years, with a predominance of untreated partners (61.5%) over treated ones (14.9%), excluding the 23.6% who had this information ignored. The variations presented from 2018 onwards stand out, resulting from the softening implemented in the notification of partner data, with an average of 23.7% of ignored information. Consequently, the diagnosis of recent congenital syphilis was found in 83.7% of newborns whose parents were not treated, in addition to 50% of cases of late infection and the vast majority of cases of stillbirths/abortion (92.6%) and deaths from the disease (78.8%). Furthermore, the non-inclusion of the partner in prenatal care (83%) contributed mainly to delays in the diagnosis of maternal syphilis, with 90.1% during delivery/curettage, 76.7% after delivery, and 77.2% of them not even identified with the disease. Conclusion: In addition to the increase in cases of congenital syphilis, there was a predominance of untreated partners, coinciding with changes in the notification criteria in 2018, which contributed to most cases of delay in maternal diagnosis, reinfection, and vertical transmission. Thus, the partner’s approach is essential to guarantee the treatment and interruption of the transmission of the disease.

Congenital Infections: Priorities and Possibilities for Resource-limited Settings.

Congenital Infections: Priorities and Possibilities for Resource-limited Settings.

Protection against Congenital CMV Infection Conferred by MVA-Vectored Subunit Vaccines Extends to a Second Pregnancy after Maternal Challenge with a Heterologous, Novel Strain Variant.

Maternal reinfection of immune women with novel human cytomegalovirus (HCMV) strains acquired during pregnancy can result in symptomatic congenital CMV (cCMV) infection. Novel animal model strategies are needed to explore vaccine-mediated protections against maternal reinfection. To investigate this in the guinea pig cytomegalovirus (GPCMV) model, a strictly in vivo-passaged workpool of a novel strain, the CIDMTR strain (dose, 1 × 107 pfu) was used to infect dams that had been challenged in a previous pregnancy with the 22122 strain, following either sham-immunization (vector only) or vaccination with MVA-vectored gB, gH/gL, or pentameric complex (PC) vaccines. Maternal DNAemia cleared by day 21 in the glycoprotein-vaccinated dams, but not in the sham-immunized dams. Mean pup birth weights were 72.85 ± 10.2, 80.0 ± 6.9, 81.4 ± 14.1, and 89.38 ± 8.4 g in sham-immunized, gB, gH/gL, and PC groups, respectively (p < 0.01 for control v. PC). Pup mortality in the sham-immunized group was 6/12 (50%), but reduced to 3/35 (8.6%) in combined vaccine groups (p = 0.0048). Vertical CIDMTR transmission occurred in 6/12 pups (50%) in the sham-vaccinated group, compared to 2/34 pups (6%) in the vaccine groups (p = 0.002). We conclude that guinea pigs immunized with vectored vaccines expressing 22122 strain-specific glycoproteins are protected after a reinfection with a novel, heterologous clinical isolate (CIDMTR) in a second pregnancy.

578 Urine cytomegalovirus shedding among seropositive pregnant women

Globally, the majority of congenital cytomegalovirus(CMV) infection is thought to occur following maternal re-infection or re-activation. We seek to characterize the rates of viral shedding during pregnancy among HIV-negative, CMV-seropositive women. Prospective cohort study of CMV-seropositive women throughout gestation at one tertiary care hospital between 9/1/2018 and 9/1/2020. Subjects eligible if positive for CMV Immunoglobulin G(IgG) during early pregnancy screening. Subjects excluded for HIV positivity. Urine samples collected at three timepoints during pregnancy. Using Immediate early 1 (IE-1) gene as indicative of the presence of CMV, DNA isolated and quantified from samples for viral load(VL) calculation: No VL detected, VL 1-2000 copies/mL (low-shedders), VL >2000 copies/mL (high-shedders). Of the 244 subjects enrolled, 54% were White, mean (standard deviation) age was 31 (5.5) years, and 61% had children living at home. More than a third also worked in healthcare or had a household member who worked in healthcare(Table 1). Of 583 urine samples tested, 307 (52.7%) had no virus detected, and 276 (47.3%) qualitatively showed evidence of CMV. Of positive samples, 252 (91.3%) were low-shedders, and 24 (8.7%) were high-shedders. The distribution was relatively evenly spread across trimesters, including delivery samples(Figure 1). Approximately half of urine samples from known CMV-seropositive women in our cohort had evidence of viral shedding, and occurred in all trimesters. Further study is needed to better understand risk factors associated with viral shedding and the clinical implications of shedding in seropositive women.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Contact tracing of syphilis-seropositive pregnant women and syphilis-infection among their male partners in Bao'an district, Shenzhen, China

BackgroundUntreated male partners are a critical source of maternal re-infection. Contact tracing is a good way to identify infection among partners and reduce risk of mother-to-child transmission related to maternal re-infection. This study aimed to analyze the current situation and related factors of contact tracing of syphilis-seropositive pregnant women and syphilis-infection among their male partners.MethodData of syphilis-seropositive pregnant women and their male partners attending clinic for syphilis-screening were obtained from the Shenzhen Program for Prevention of Congenital Syphilis. Contact tracing rate of syphilis-seropositive pregnant women and syphilis prevalence among male partners were counted, and related factors were also analyzed using a random-effects logistic regression model.ResultOf the 1299 syphilis-seropositive pregnant women, 74.1% (963/1299) had their male partners receiving syphilis-screening and 19.1% (184/963) of male partners were syphilis-infected. For pregnant women, being divorced (adjusted odds ratio [AOR] =0.39; 95%CI: 0.17–0.87), seeking for emergency services at their first antenatal clinics visits (AOR = 0.58; 95%CI: 0.44–0.77), reporting willingness to notify partner(AOR = 7.65; 95%CI: 4.69–12.49), multi-partners (AOR = 1.38; 95%CI:1.03–1.86) and having a history of drug abuse (AOR = 0.37; 95%CI: 0.14–1.00)were independently associated with successful contact tracing. For male partners, of minority ethnicity (AOR = 4.15; 95%CI: 1.66–10.34), age at first sex>20(AOR = 0.57; 95%CI: 0.37–0.87), reporting multi-partners (AOR = 1.60; 95%CI: 1.04–2.46), having a history of drug abuse (AOR = 4.07; 95%CI: 1.31–12.64) were independently associated with syphilis-infection. In addition, pregnant women with TRUST titer ≥1:8 (AOR = 2.81; 95%CI: 1.87–4.21), having a history of adverse pregnancy outcomes (AOR = 1.70; 95%CI: 1.14–2.53), reporting multi-partners (AOR = 0.43; 95%CI: 0.29–0.64) and reporting the current partner as the source of syphilis (AOR = 5.05; 95%CI: 2.82–9.03) were independently associated with partners’ syphilis-infection.ConclusionContact tracing is feasible and effective in identifying syphilis-infected partners among syphilis-seropositive pregnant women. Contact tracing is associated with many factors such as women’s marital status, services at their first antenatal clinics visit and willingness of partner notification. Partners’ ethnicity, age at first sex, multi-partners and history of drug abuse as well as women’s levels of TRUST titer were associated with partners’ syphilis-infection.

Cytomegalovirus seroprevalence in pregnant women in the western region of Romania: A large-scale study.

Cytomegalovirus (CMV) infection is the most common congenital infection worldwide, and remains a significant cause of the neurological deficiency and sensory deafness in developed countries. Maternal primary infection, reactivation or reinfection during pregnancy may lead to fetal infection and congenital CMV syndrome. The purpose of this study was to analyze the CMV seroprevalence according to demographic features of pregnant women in western Romania as well as the evolution of CMV immunity in two time intervals. IgG anti-CMV antibodies were tested in sera of 8,951 pregnant women during two successive intervals: 2008-2010 (n=1466) and 2015-2018 (n=7485). The CMV seroprevalence in women of reproductive age decreased from 94.6 to 91.80% in the last decade. The seroprevalence was higher in women from rural areas compared with those from urban areas. These results show that the western region of Romania has a low-risk profile for primary CMV infection during pregnancy due to a large number of seropositive women. However, this risk has increased in the last ten years, from 5.4 to 8.2%, which may show the need to implement a national screening program.

Fetal therapies for cytomegalovirus: What we tell prospective parents.

Congenital CMV is the most common congenital infection in the developed world. Infection results in congenital disease ranging from asymptomatic infection to severe neurodevelopmental impairment, and occasionally fetal or neonatal death. Fetal infection can occur through maternal-fetal transmission during primary maternal infection or maternal reactivation or re-infection. Awareness among maternal health care providers and parents is low. The prevention of maternal CMV infection currently relies on hygiene measures, with no effective CMV vaccine or prophylactic therapies. No licensed treatment options are available to prevent maternal-fetal transmission or fetal disease. Hyperimmunoglobulin and valaciclovir have been investigated for prevention of maternal-fetal transmission or fetal treatment, with some evidence supporting consideration of maternal administration of hyperimmunoglobulin or valaciclovir therapy in certain circumstances. This article outlines the clinical evidence regarding proven preventative behavioral measures and experimental hyperimmunoglobulin and valaciclovir therapies, that is structured around common questions asked by pregnant women about CMV infection. It is aimed to help maternity health care providers counsel prospective parents about congenital CMV disease and the preventative and therapeutic strategies currently available.

Natural History of Congenital Cytomegalovirus Infection in Highly Seropositive Populations.

Maternal preconceptional cytomegalovirus (CMV) immunity does not protect the fetus from acquiring congenital CMV infection (cCMV). Nonprimary infections due to recurrence of latent infections or reinfection with new virus strains during pregnancy can result in fetal infection. Because the prevalence of cCMV increases with increasing maternal CMV seroprevalence, the vast majority of the cases of cCMV throughout the world follow nonprimary maternal infections and is more common in individuals of lower socioeconomic background. Horizontal exposures to persons shedding virus in bodily secretions (young children, sexual activity, household crowding, low income) probably increase the risk of acquisition of an exogenous nonprimary CMV infection and fetal transmission. In addition, more frequent acquisition of new antibody reactivities in transmitter mothers suggest that maternal reinfection by new viral strains could be a major source of congenital infection in such populations. However, the exact frequency of CMV nonprimary infection in seroimmune women during pregnancy and the rate of intrauterine transmission in these women are yet to be defined. Usually, the birth prevalence of cCMV is high (≥7:1000) in highly seropositive populations. There is increasing evidence that the frequency and severity of the clinical and laboratory abnormalities in infants with congenital CMV infection born to mothers with nonprimary CMV infection are similar to infants born after a primary maternal infection. This is particularly true for sensorineural hearing loss, which contributes to one third of all early-onset hearing loss in seropositive populations. This brief overview will discuss the need for more research to better clarify the natural history of cCMV in highly seropositive populations, which, in almost all populations, remains incompletely defined.

Nonprimary Maternal Cytomegalovirus Infection After Viral Shedding in Infants.

Most infants with congenital Cytomegalovirus (CMV) infection are born to seropositive women as a result of maternal CMV nonprimary infection (reinfection or reactivation). Although infected children are known to transmit CMV to their seronegative mothers, the frequency and magnitude of nonprimary maternal CMV infection after exposure to viral shedding by children in their household have not been characterized. A cohort of Ugandan newborns and their mothers were tested weekly for CMV by quantitative polymerase chain reaction of oral swabs. Infant primary infection and maternal nonprimary infection were defined by the onset of persistent high-level oral CMV shedding. Strain-specific antibody testing was used to assess maternal reinfection. Cox regression models with time-dependent covariates were used to evaluate risk factors for nonprimary maternal infection. Nonprimary CMV infection occurred in 15 of 30 mothers, all after primary infection of their infants by a median of 6 weeks (range: 1-10) in contrast to none of the mothers of uninfected infants. The median duration of maternal oral shedding lasted 18 weeks (range: 4-42) reaching a median maximum viral load of 4.69 log copies/mL (range: 3.22-5.64). Previous-week infant CMV oral quantities strongly predicted maternal nonprimary infection (hazard ratio: 2.32 per log10 DNA copies/swab increase; 95% confidence interval: 1.63-3.31). Maternal nonprimary infections were not associated with changes in strain-specific antibody responses. Nonprimary CMV infection was common in mothers after primary infection in their infants, consistent with infant-to-mother transmission. Because infants frequently acquire CMV from their mothers, for example, through breast milk, this suggests the possibility of "ping-pong" infections. Additional research is needed to characterize the antigenic and genotypic strains transmitted among children and their mothers.

Is the mixture of human cytomegalovirus genotypes frequent in infants with congenital infection at birth in a high seroprevalence population?

It is still not well known, in a population with high human cytomegalovirus (HCMV) seroprevalence, whether a child with congenital infection harbors multiple viral strains at birth, and whether the prolonged viral excretion in these children is secondary to the persistence of the same viral strain. To verify the genomic diversity of HCMV detected in congenitally infected children, the nucleotide viral sequences from urine and/or saliva obtained at birth from 14 newborns with congenital infection and breast milk obtained from mothers of 5 of these children were analyzed. Among the 14 children, 10 had sequential samples until the median age of 10 months. The viral nucleotide sequences in the breast milk were compared with those identified in the respective children at birth. The differentiation of viral strains was based on the variability of 3 regions of viral genes (UL55/gB, UL144, and UL73/gN). In 13/14 children (92.8%), a single genotype was observed at birth. Different viral genotypes were found in 1 child (7.2%). Among the sequential samples from 10 children, the same genotype obtained at birth was detected in 9/10 (90%), and in 1 of them (10%), a genotype change in the urine was found. More than 1 HCMV strain in milk was observed in 2 mothers (2/5, 40%). In a population with high seroprevalence, a single genotype was found in the majority of infected children. Reinfection did not frequently occur in the first months of life. Maternal reinfection does not seem to be a rare event in transmitter mothers.

Advancing Our Understanding of Protective Maternal Immunity as a Guide for Development of Vaccines To Reduce Congenital Cytomegalovirus Infections.

Human cytomegalovirus (HCMV) is the most common congenitally transmitted pathogen worldwide, impacting an estimated 1 million newborns annually. Congenital HCMV (cCMV) infection is a major global contributor to long-term neurologic deficits, including deafness, microcephaly, and neurodevelopmental delay, as well as to fetal loss and occasional infant mortality. Accordingly, design of a maternal vaccine to prevent cCMV continues to be a top public health priority. Nevertheless, we remain without a licensed vaccine. Maternal immunity provides partial protection, as the risk of vertical HCMV transmission from chronically infected mothers is reduced compared to settings in which the mother is newly infected during pregnancy. Therefore, an understanding of the maternal immune correlates of protection against cCMV is critical to informing design of an efficacious maternal vaccine. Although vaccine development is being assiduously pursued by a large number of pharmaceutical manufacturers, biotechnology organizations, and academic researchers, some pessimism has been expressed regarding the issue of whether a vaccine to protect against cCMV is possible. This pessimism is based on observations that natural immunity is not completely protective against maternal reinfection and congenital transmission. However, we assert that optimism regarding vaccine development is indeed justified, on the basis of accruing evidence of immune correlates of protection-readily achievable by vaccination-that are associated with reduced transmission of HCMV to the fetus in seronegative women. In light of the substantial burden on society conferred by cCMV infection, even a modest reduction in the occurrence of this fetal disease is an important public health goal and justifies aggressive clinical evaluation of vaccines currently in the pipeline.

Pneumopathie congénitale à cytomégalovirus chez un nouveau-né à terme né de mère séropositive pour le VIH

Cytomegalovirus (CMV) is one of the most common intrauterine infections, affecting approximately 1% of all live births. There are few reports on congenital CMV infections manifesting as isolated pneumonitis. We report a case of congenital CMV with neonatal respiratory distress affecting an HIV-exposed uninfected infant. This infant required noninvasive ventilation beginning within the first 15min of life. The initial chest X-ray showed diffuse bilateral ground-glass opacifications. Bacterial infection, meconium aspiration and hyaline membrane disease were excluded. Salivary quantitative CMV PCR was positive (2,342,261IU/mL) and serum viral load for CMV was low (476IU/mL). Bronchoalveolar lavage (BAL) performed on day 12 for quantitative CMV PCR was significantly positive (1,045,942IU/mL). Intravenous ganciclovir treatment was started on day 14 (7.5mg/kg/12h) for 2weeks and oral valganciclovir (15mg/kg/12h) was given for 4weeks afterwards. Ventilatory support was stopped on day18. HIV serum viral load was negative on day30. Congenital CMV infection can present as isolated pneumonitis with persistent neonatal respiratory symptoms, emphysematous lung disease, or persistent pulmonary hypertension. If this diagnosis is suspected, and even if CMV viremia remains low, BAL with quantitative CMV PCR must be performed to ascertain the diagnosis and indicate antiviral treatment. HIV-exposed uninfected infants have higher rates of congenital CMV infection when the mother's CD4 rate is<200/mm3. Most cases of CMV transmission in HIV-exposed uninfected infants have occurred by maternal endogenous reactivation or reinfection.

Human Cytomegalovirus Modulates Expression of Noncanonical Wnt Receptor ROR2 To Alter Trophoblast Migration.

Maternal primary cytomegalovirus (CMV) infection, reactivation, or reinfection with a different viral strain may cause fetal injury and adverse pregnancy outcomes. Increasing evidence indicates that fetal injury results not only from direct viral cytopathic damage to the CMV-infected fetus but also from indirect effects through placental infection and dysfunction. CMV alters Wingless (Wnt) signaling, an essential cellular pathway involved in placentation, as evidenced by reduced transcription of canonical Wnt target genes and decreased Wnt3a-induced trophoblast migration. Whether CMV affects the noncanonical Wnt signaling pathway has been unclear. This study demonstrates for the first time that CMV infection inhibits Wnt5a-stimulated migration of human SGHPL-4 trophoblasts and that inhibition of the pathway restores normal migration of CMV-infected cells. Western blot and real-time PCR analyses show increased expression of noncanonical Wnt receptor ROR2 in CMV-infected trophoblasts. Mimicking the CMV-induced ROR2 protein expression via ectopic expression inhibited Wnt5a-induced trophoblast migration and reduced T cell-specific factor (TCF)/lymphoid enhancer-binding factor (LEF)-mediated transcription as measured using luciferase reporter assays. Gene silencing using small interfering RNA (siRNA) duplexes decreased ROR2 transcript and protein levels. In contrast, proliferation of SGHPL-4 trophoblasts, measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was not affected. The siRNA-mediated downregulation of ROR2 in trophoblasts rescued CMV-induced reduction in trophoblast migration. These data suggest a mechanism where CMV alters the expression of the Wnt receptor ROR2 to alter Wnt5a-mediated signaling and inhibit trophoblast motility. Inhibition of this mechanism may be a target for therapeutic intervention for CMV-induced placental damage and consequent fetal damage in congenital CMV infections. Maternal primary cytomegalovirus (CMV) infection, reactivation, or reinfection with a different viral strain may cause fetal injury and adverse pregnancy outcomes. Increasing evidence indicates that fetal injury results not only from direct viral cytopathic damage to the CMV-infected fetus but also from indirect effects through placental infection and placental dysfunction. No effective therapy is currently proven to prevent or treat congenital CMV infection. Understanding the molecular underpinnings of CMV infection of the placenta is essential for therapeutic innovations and vaccine design. CMV alters canonical Wingless (Wnt) signaling, an essential cellular pathway involved in placental development. This study suggests a mechanism in which CMV alters the expression of noncanonical Wnt receptor ROR2 to alter motility of placental cells, which has important implications in the pathogenesis of CMV-induced placental dysfunction. Inhibition of this mechanism may be a target for therapeutic intervention for CMV-induced placental damage and consequent fetal damage in congenital CMV infection.

Prevention of Maternal–Fetal Transmission of Cytomegalovirus

Reported maternal-to-fetal rates of primary cytomegalovirus (CMV) infection during pregnancy have been between 30% and 50%. The highest rate of symptomatic congenital infection and sequelae occurs in about 25% of infected infants born of mothers with a primary infection during pregnancy. Symptomatic infants demonstrate a constellation of clinical features that reflect placental dysfunction and probable viral infection of the central nervous system of the fetus. In the United States, we estimate that about 8000 affected infants are born each year. Two options may be available to prevent or treat maternal CMV infection during pregnancy, especially for women with exposure to young children in the home. The first is hygienic intervention. Two studies support the simplicity, harmlessness, and effectiveness of hygienic intervention to prevent child-to-mother transmission of CMV among high-risk pregnant women who know they are susceptible. The second is CMV immunoglobulin. A meta-analysis of 2 clinical trials showed an efficacy of 50% if immunoglobulin is given to pregnant women who have acquired a primary CMV infection during pregnancy. These results mean that seronegative pregnant women have options to prevent fetal infection.

Cytomegalovirus (CMV) glycoprotein H-based serological analysis in Japanese healthy pregnant women, and in neonates with congenital CMV infection and their mothers

BackgroundCongenital cytomegalovirus (CMV) infection is caused by maternal primary infection as well as CMV reinfection or reactivation during pregnancy, although differences in the clinical impact between these modes of infection remain to be clarified. ObjectivesTo investigate the latest prevalence and risk of multiple CMV infection in healthy pregnant women, as well as the types of maternal CMV infection associated with congenital CMV infection. Study designSeroprevalence against CMV and IgG subclasses were determined in 344 serum samples from healthy pregnant women in Japan. CMV genotype and serotype were also determined in 18 pairs of mothers and neonates with congenital CMV infection identified in our CMV screening program. ResultsThirty-two percent of the pregnant women were seronegative, while 66% of CMV seropositive women had IgG3 antibodies against one epitope on glycoprotein H (gH) as the major subclass, and 52% had IgG1 antibodies against one epitope on glycoprotein B (gB). Only a single genotype determined by CMV gH neutralizing epitope was found in the urine from the 18 neonates with congenital CMV infection, even though one case possessed antibodies against multiple CMV strains. In that case, the antibodies against the strain not detected in the urine from the infant disappeared within one month after birth, whereas the antibodies against the infecting CMV strain continued to be detected at 12 months after birth. ConclusionsTwo (11%) of 18 cases of congenital CMV infection occurred via maternal CMV reinfection. Maternal humoral immunity did not prevent congenital CMV infection with another gH subtype.

Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection

Congenital cytomegalovirus (CMV) infections are a leading cause of sensorineural hearing loss (SNHL) and neurological impairment. Congenital transmission of CMV can occur with maternal primary infection, reactivation, or reinfection during pregnancy. We reviewed studies of CMV shedding in bodily fluids (defined as CMV detected by culture or CMV DNA detected by polymerase chain reaction). Following diagnosis at birth, children with congenital CMV infection exhibited the highest prevalences of CMV shedding (median = 80%, number of sample population prevalences [N] = 6) and duration of shedding, with a steep decline by age five. Healthy children attending day care shed more frequently (median = 23%, N = 24) than healthy children not attending day care (median = 12%, N = 11). Peak shedding prevalences in children occurred at 1-2 years of age, confirming that young children are the key transmission risk for pregnant women. CMV shedding among children was more prevalent in urine specimens than in oral secretions (median prevalence difference = 11.5%, N = 12). Adults with risk factors such as STD clinic attendance had higher shedding prevalences (median = 22%, N = 20) than adults without risk factors (median = 7%, N = 44). In adults with risk factors, CMV was shed more frequently in urine; in adults without risk factors genital shedding was most common. The prevalence of CMV shedding in nine sample populations of pregnant women increased with advancing gestation. In seven sample populations of children with congenital CMV infection, higher viral load at birth was consistently associated with an elevated risk of SNHL. Higher CMV viral load at birth also consistently correlated with the presence of symptoms of congenital CMV at birth. Published 2011. This article is a US Government work and is in the public domain in the USA.

Congenital Cytomegalovirus Infection Manifesting as Neonatal Persistent Pulmonary Hypertension: Report of Two Cases

Various neonatal symptoms can lead to a diagnosis of congenital CMV infection. We report two cases of persistent pulmonary hypertension in relation with congenital CMV infection following maternal primary infection and reinfection, respectively. Both infants had severe refractory hypoxemia, requiring high-frequency ventilation, inhaled nitric oxide and inotropic support. One of them required extracorporeal membrane oxygenation for five days. Ganciclovir therapy was attempted in the two cases on day 12 postnatal. One of the infant died on day 15 postnatal. The other survived and is developing uneventfully at 15 months of age. Conclusion: Neonatal persistent pulmonary hypertension can be the consequence of congenital CMV infection. Intensive respiratory support and IV ganciclovir are indicated in case of life-threatening condition.

Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus-immune maternal population

To determine contribution of reinfection with new strains of cytomegalovirus in cytomegalovirus seromimmune women to incidence of congenital cytomegalovirus infection. In 7848 women studied prospectively for congenital cytomegalovirus infection from a population with near universal cytomegalovirus seroimmunity, sera from 40 mothers of congenitally infected infants and 109 mothers of uninfected newborns were analyzed for strain-specific anticytomegalovirus antibodies. All women were cytomegalovirus seroimmune at first prenatal visit. Reactivity for 2 cytomegalovirus strains was found in 14 of 40 study mothers and in 17 of 109 control mothers at first prenatal visit (P = .009). Seven of 40 (17.5%) study women and 5 of 109 (4.6%) controls (P = .002) acquired antibodies reactive with new cytomegalovirus strains during pregnancy. Evidence of infection with more than 1 strain of cytomegalovirus before or during current pregnancy occurred in 21 of 40 study mothers and 22 of 109 controls (P < .0001). Maternal reinfection by new strains of cytomegalovirus is a major source of congenital infection in this population.